EXTRACELLULAR SIMIAN-VIRUS-40 INDUCES AN ERK MAP KINASE-INDEPENDENT SIGNALING PATHWAY THAT ACTIVATES PRIMARY RESPONSE GENES AND PROMOTES VIRUS ENTRY/

Simian virus 40 (SV40) binding to growth-arrested cells activated an i ntracellular signalling pathway that induced the up-regulation of the primary response genes c-myc, c-jun and c-sis within 30 min and of IE within 90 min, The up-regulation of the primary response genes occurre d in the presence of cycloheximide and when UV-inactivated SV40 was ad sorbed to cells, SV40 binding did not activate Raf or mitogen-activate d protein kinase (MAP/ERK1), or mobilize intracellular Ca2+, The SV40- induced up-regulation of c-myc and c-jun was blocked by the tyrosine k inase inhibitor, genistein, and by the protein kinase C (PKC) inhibito r, calphostin C, but not by expression of the MAP kinase-specific phos phatase, MKP-1. These results suggest that the SV40-induced signalling pathway includes the activities of a tyrosine kinase and a Ca2+-indep endent isoform of PKC, but not of Raf or MAP kinase, Finally, SV40 inf ectious entry into cells was specifically and reversibly blocked by ge nistein.